In aging and many disease states, the energy production capacity of the body’s cells is diminished. The mitochondria are the structures within the cell responsible for generating energy from oxygen and nutrients. If their number is reduced or their function is impaired, free radicals are produced and damaging toxins accumulate in the cells. These toxins further damage the mitochondria and impair other aspects of cellular function. Many of the most common health problems, such as obesity, diabetes, and many problems associated with aging, arise from problems in cellular energy production. As one group of researchers has put this, "[a]ging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan."¹ Another has observed, "[m]itochondrial biogenesis [the creation of new mitochondria] is a key physiological process that is required for normal growth and development and for maintenance of ongoing cellular energy requirements during aging."² These observations link two key aspects of mitochondrial health, preventing and removing damaged mitochondria (mitophagy) and creating new mitochondria (mitogenesis).

Although the importance of the mitochondria as a central point of health has been accepted for decades, over the last few years the understanding of the mechanisms involved has changed significantly. Twenty or ten years ago, antioxidants and the free radical theory of aging largely dominated thinking. Today, the importance of mitochondrial biology linking basic aspects of aging and the pathogenesis of age-related diseases remains strong, yet the emphasis has changed. The focus has moved to mitochondrial biogenesis and turnover, energy sensing, apoptosis, senescence, and calcium dynamics.³

What Promotes Mitochondrial Biogenesis?
The body maintains a complex network of sensors and signaling functions to maintain stability despite a constantly changing environment and numerous challenges. Of special note is the concept of hormesis, meaning a state in which mild stress leads to compensation that improves the ability of the body to respond in the future to similar challenges. It turns out that many of the approaches that are associated with longevity and healthy aging promote hormesis. In terms of mitochondria biogenesis, these include caloric restriction, certain nutrient restrictions or shortages, caloric restriction mimetics, and exercise.

Many of the mechanisms that activate mitochondrial biogenesis in the face of hormesis have been elucidated. Keeping in mind that there always must be a balance between the elimination of worn-out and defective mitochondria and the generation of new ones, the activators of both actions can overlap. For instance, low energy levels (caloric restriction) and increased reactive oxygen species/free radicals can promote the activity of special cellular control points. These include activating metabolic sensors such as AMP kinase/ AMPK (adenosine monophosphate kinase) and the protein known as SIRT1 (sirtuin 1, i.e., silent mating type information regulation 2 homolog 1). Activated AMPK is an indicator that cellular energy is low and serves as a trigger to increase energy production. It inhibits insulin/IGF-1/mTOR signaling, all of which are anabolic and can lead not just to tissue production, such as muscle growth, but also to fat storage. Along with SIRT1, AMPK activates the biogenesis of new mitochondria to enable the cell to generate more energy. At the same time, activated AMPK and SIRT1 increase the activity of a tumor suppressor that induces mitophagy. The balance of the dual activations replaces defective mitochondria with newly formed functionally competent mitochondria.

A key to health and healthy aging is to regulate the catabolic processes via controlled amounts and types of stressors such that worn out mitochondria are removed without overshooting the mark and reducing overall cellular and tissue functionality. The most successful way to maintain this balance is to follow the body’s own natural metabolic signals rather than to attempt to override the body’s checkpoints. AMPK and SIRT1 ultimately are energy/nutrient sensors or control points. Hence rather than attempting to manipulate these directly, it likely is safer and ultimately more effective to address the factors in the cell that these sensors sense. The recent attention in the issue of aging to the role of NAD+ (the oxidized form of nicotinamide adenine dinucleotide) is a good example of this principle. Directions coming from the nucleus of the cell that help to regulate the normal production of NAD+ and the ratio between distinct pools found in the cytoplasm and in the mitochondria decline with age. The changes in the NAD+ from the nucleus lead to a disruption on the mitochondrial side. In terms of energy production, it is a bit like losing a link or two in the timing chain on your car engine with a resultant reduction in engine efficiency. To date, attempts to increase NAD+ in cells via supplementation with precursors have not proven particularly successful. Major benefits have been demonstrated in animal models only in the already seriously metabolically impaired or the relatively old. Recent research on oral supplementation has led to at least one extremely difficult article which, at least in this author’s opinion, delivers more smoke than heat.4,5 There is, however, an argument to the effect that supplementing together both nicotinamide riboside (a NAD+ precursor) and a sirtuin activator, such as pterostilbene, may prove to be more successful.

It turns out that there are key points in normal cellular energy generation processes that strongly influence the NAD+ pools available for the cell to draw upon and the rate at which NAD+ can be replaced in these pools. Aging has been shown to promote the decline of nuclear and mitochondrial NAD+ levels and to increase the risk of cancer along with components of the metabolic syndrome. It is significant that the risks of these conditions can be reduced in tandem. Three places to start are 1) the pyruvate dehydrogenase complex, 2) the tricarboxylic acid cycle (TCA cycle) also known as the Krebs Cycle, and 3) the malate shuttle. A fourth junction is Complex I of the electron transport system, again, in the mitochondria.6 Manipulation of steps (1) and (2) already is being used in cancer treatment.7 Readily available dietary supplements can influence all four of these metabolic bottlenecks.

Supplements for Promoting Mitochondrial Biogenesis
Medicine has started to pay a great deal of attention to effecting mitochondrial biogenesis through not just drugs, but also dietary supplements. Those interested should go online and look up "Mitochondrial Biogenesis: Pharmacological Approaches" in Current Pharmaceutical Design, 2014, Vol. 20, No. 35. Quite a few options are mentioned, including well known compounds, such as R-lipoic acid (including with L-carnitine), quercetin and resveratrol, along with still obscure supplements, including various triterpenoids and the Indian herb Bacopa monnieri.

Pomegranate, French White Oak and Walnuts
The pomegranate, with its distinctive scarlet rind (pericarp) and vibrantly colored seed cases (arils), is one of the oldest cultivated fruits in the world. This exotic fruit features prominently in religious texts and mythological tales and has been revered through the ages for its medicinal properties. An image of a pomegranate even can be found on the shield of the British Royal College of Medicine. Numerous studies have demonstrated the benefits of the fruit for cardiovascular health with other benefits suggested in areas ranging from arthritis to stability of cell replication to bone health. Now a study in Nature Medicine (July 2016) has uncovered perhaps the most important benefit of all, the ability of pomegranate compounds (ellagitannins) transformed by gut bacteria to protect the mitochondria of the muscles and perhaps other tissues against the ravages of aging. The mitochondria are the energy generators of the cells and the weakening of this energy generating function in an increasing percentage of mitochondria as we age is a primary source of physical decline over the years. Urolithin A, a byproduct of gut bacterial action on pomegranate compounds, allows the body to recycle defective mitochondria and thereby slow or even reverse for a time some of the major aspects of aging. The lifespan in a nematode model of aging was increased by more than 45 percent. Older mice in a rodent model of aging exhibited 42 percent better exercise endurance. Younger mice also realized several significant benefits.⁸

Beginning almost three decades ago, there were numerous speculations in the research world regarding the so-called "French Paradox" in which the French consumed quite large amounts of saturated fat in the form of butter and cheese, yet consistently experienced much lower rates of cardiovascular disease than did Americans. Not only that, the French, especially in the southwest of the country, typically led longer lives even in the areas noted for consuming large amounts of goose fat and pate de foie gras, which is to say, not just the Mediterranean diet based on olive oil, etc. One hypothesis put forth very early on was that it was the French consumption of red wine that protected them. It was thought that red wine components, including anthocyanidins, proanthocyanidins and resveratrol, are the protective compounds. Not considered until recently is that French red wines traditionally have been aged in casks made from white oak (Quercus robur). White oak contains roburin A, a dimeric ellagitannin related chemically to punicalagin. Human data show relatively good absorption and conversion of roburins into substances including urolithin A and ellagic acid—as compared with ellagitannins in general, which evidence only poor absorption. Hence, the benefits of good red wine traditionally produced and good cognac (also aged in oak barrels) involve urolithin A. Notably, the benefits of roburins, most likely derived from the conversion to urolithin A, go beyond mitophagy to include ribosomes, referring to cell components that translate DNA instructions into specific cellular proteins.^9,10,11,12

Other sources of ellagitannins have been shown to lead to the production of urolithin A by bacteria in the human gut. Not surprisingly, sources of ellagitannins are foods long associated with good health longevity, including not just pomegranate and oak-aged red wine, but also walnuts (and a smattering of other nuts), strawberries, raspberries, blackberries, cloudberries and even black tea in small amounts.

Exercise and Pyrroloquinoline Quinone (PQQ)
Peroxisome proliferator-activated receptor gamma coactivator (PGC-1á) is the master regulator of mitochondrial biogenesis.¹³ Exercise is perhaps the most significant activator of PGC-1á that most individuals can access. Exercise, furthermore promotes mitochondrial biogenesis through a number of other pathways, especially endurance and interval training.¹⁴

There are non-exercise options. You can’t take PGC-1á orally because it is a large protein molecule which does not survive digestion. PQQ is a small molecule that is available when ingested and that increases circulating PGC-1á. PQQ supplementation leads to more mitochondria and more functional mitochondria.¹⁵

Fasting, Ketogenic Diets and Fasting-Mimicking Supplements As already discussed, fasting promotes mitochondrial biogenesis by AMPK activation.¹⁶ AMPK senses the energy status of the cell and responds both to acute shortages, such as that induced by exercise, and to chronic shortages, such as from fasting. Probably due to an overall reduction in metabolic rate, chronic caloric restriction (as opposed to intermittent fasting) contributes to the health of mitochondria rather than biogenesis.¹⁷ The robustness of AMPK response decreases with age.¹⁸

Ketogenic diets (very low carbohydrate diets) also promote increases in mitochondria.¹⁹ Few individuals are willing or able to follow ketogenic diets chronically just as few individuals are willing to undergo routine fasts. Fasting-mimicking supplements offer an alternative approach. The dietary supplement (-)–hydroxycitric acid (HCA) is the best researched of these compounds. (Keep in mind that there is a vast difference in the efficacy of commercially available forms.²⁰) Researchers have proposed that HCA used properly can activate mitochondrial uncoupling proteins and related effects.²¹

Furthermore, according to a study published in the journal Free Radical Research in 2014, HCA improves antioxidant status and mitochondrial function plus reduces inflammation in fat cells.²² Inflammation is linked to the metabolic syndrome at the cellular level by way of damage to the antioxidant enzyme system (e.g., superoxide dismutase, glutathione peroxidase, glutathione reductase) and mitochondria. This damage, in turn, propagates further production of pro-inflammatory mediators (e.g., TNF-á, MCP-1, IFN-ã, IL-10, IL-6, IL-1â). HCA protected fat cells from ER stress by improving the antioxidant status to reduce oxidative stress (i.e., reduce ROS) and improve the function of the mitochondria to short circuit an ER stress—inflammation loop in these cells. Reducing TNF-á is important in that doing so removes a major impediment to mitochondrial biogenesis.²³

Other Supplements to Promote Mitochondrial Biogenesis

Scholarly reviews looking at natural compounds such as those that are found in anti-aging diets suggest yet other supplements to promote mitobiogenesis. For instance, it turns out that hydroxytyrosol, the most potent and abundant antioxidant polyphenol in olives and virgin olive oil, is a potent activator of AMPK and an effective nutrient for stimulating mitochondrial biogenesis and function via what is known as the PGC-1á pathway.²⁴ Another herb with anti-aging effect, this time by activating the malate shuttle mechanism mentioned above, is rock lotus (Shi Lian Hua). This herb has been described in detail in this magazine in the article, "Uncovering the Longevity Secrets of the ROCK LOTUS."²⁵

Conclusion
It is possible to improve the functional capacity of the mitochondria through dietary practices, exercise and supplements. Indeed, a number of compounds have been identified by researchers as mitochondrial nutrients. These compounds work together to increase the efficiency of energy production, to reduce the generation of free radicals, and so forth and so on. Likewise, these nutrients have been shown to improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the ageassociated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. Perhaps best of all, the body can be encouraged both to remove damaged mitochondria (mitophagy) and to create new ones, which is to say, mitochondrial biogenesis.

References:

1. López-Lluch G, Irusta PM, Navas P, de Cabo R. Mitochondrial biogenesis and healthy aging. Exp Gerontol. 2008 Sep;43(9):813–9.
2. Stefano GB, Kim C, Mantione K, Casares F, Kream RM. Targeting mitochondrial biogenesis for promoting health. Med Sci Monit. 2012 Mar;18(3):SC1-
3. Gonzalez-Freire M, de Cabo R, Bernier M, Sollott SJ, Fabbri E, Navas P, Ferrucci L. Reconsidering the Role of Mitochondria in Aging. J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1334-42.
4. Trammell SA, Schmidt MS, Weidemann BJ, Redpath P, Jaksch F, Dellinger RW, Li Z, Abel ED, Migaud ME, Brenner C. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nat Commun. 2016 Oct 10;7:12948.
5. Mitteldorf J. Nicotinamide Riboside —Where’s the Beef? http://joshmitteldorf.scienceblog.com/2014/11/17/nicotinamide-riboside-wheres-thebeef/.
6. Yang Y, Sauve AA. NAD+ metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta. 2016 Dec;1864(12):1787– 1800.
7. Schwartz L, Buhler L, Icard P, Lincet H, Steyaert JM. Metabolic treatment of cancer: intermediate results of a prospective case series. Anticancer Res.2014 Feb;34(2):973–80.
8. Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med.2016 Aug;22(8):879-88.
9. Pellegrini L, Belcaro G, Dugall M, Corsi M, Luzzi R, Hosoi M. Supplementary management of functional, temporary alcoholic hepatic damage with Robuvit® (French oak wood extract). Minerva Gastroenterol Dietol. 2016 Sep;62(3):245–52.
10. Vinciguerra MG, Belcaro G, Cacchio M. Robuvit® and endurance in triathlon: improvements in training performance, recovery and oxidative stress. Minerva Cardioangiol. 2015 Oct;63(5):403–9.
11. Országhová Z, Waczulíková I, Burki C, Rohdewald P, Ïuraèková Z. An Effect of Oak-Wood Extract (Robuvit®) on Energy State of Healthy Adults-A Pilot Study. Phytother Res. 2015 Aug;29(8):1219–24.
12. Natella F, Leoni G, Maldini M, Natarelli L, Comitato R, Schonlau F, Virgili F, Canali R. Absorption, metabolism, and effects at transcriptome level of a standardized French oak wood extract, Robuvit, in healthy volunteers: pilot study. J Agric Food Chem. 2014 Jan 15;62(2):443–53.
13. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res. 2008 Jul 15;79(2):208–17.
14. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO. Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression. J Biol Chem. 2007 Jan 5;282(1):194–9.
15. Bauerly K, Harris C, Chowanadisai W, Graham J, Havel PJ, Tchaparian E, Satre M, Karliner JS, Rucker RB. Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS One.2011;6(7):e21779.
16. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI. AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15983–7.
17. Lee CM, Aspnes LE, Chung SS, Weindruch R, Aiken JM. Influences of caloric restriction on age-associated skeletal muscle fiber characteristics and mitochondrial changes in rats and mice. Ann N Y Acad Sci. 1998 Nov 20;854:182–91.
18. Jornayvaz FR, Shulman GI. Regulation of mitochondrial biogenesis. Essays Biochem. 2010;47:69–84.
19. Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007 Jan;48(1):43–58.
20. Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG. Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metab(Lond). 2005 Sep 13;2:23.
21. McCarty MF. High mitochondrial redox potential may promote induction and activation of UCP2 in hepatocytes during hepatothermic therapy. Med Hypotheses.2005;64(6):1216–9.
22. Nisha VM, Priyanka A, Anusree SS, Raghu KG. (-)–Hydroxycitric acid attenuates endoplasmic reticulum stress-mediated alterations in 3T3-L1 adipocytes by protecting mitochondria and downregulating inflammatory markers. Free Radic Res.2014 Nov;48(11):1386-96.
23. Valerio A, Cardile A, Cozzi V, Bracale R, Tedesco L, Pisconti A, Palomba L, Cantoni O, Clementi E, Moncada S, Carruba MO, Nisoli E. TNFalpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. J Clin Invest. 2006 Oct;116(10):2791–8.
24. Liu J, Shen W, Zhao B, Wang Y, Wertz K, Weber P, Zhang P. Targeting mitochondrial biogenesis for preventing and treating insulin resistance in diabetes and obesity: Hope from natural mitochondrial nutrients. Adv Drug Deliv Rev. 2009 Nov 30;61(14):1343–52.
25. http://www.totalhealthmagazine.com/Anti-Aging/Uncovering-the-Longevity-Secrets-of-the-ROCK-LOTUS.html.

An antibiotic might be described as an antibacterial agent that inhibits bacterial growth or kills bacteria. However, colds and many other upper respiratory infections, as well as some ear infections, are caused by viruses, not bacteria. If antibiotics are used too often for things they can’t treat—like colds or other viral infections—they can stop working effectively against bacterial infections. This phenomenon is known as antibiotic resistance, and is a direct result of antibiotic overuse.¹ As it currently stands, antibiotic overuse represents a significant health risk to modern society. This article will examine antibiotic overuse, as well as the use of herbal medicines that may present a viable alternative to the use of antibiotics or when antibiotics are not indicated.

A Historical Perspective
At the beginning of the 20th century, illnesses caused by infectious diseases ranked as the most common cause of death in North America. By the middle of the century, the diagnosis, prevention, and management of infectious diseases had advanced dramatically, raising false hopes that many infectious diseases would be eliminated by the end of the 20th century. Unfortunately, clinicians, public health officials, and microbiologists have confronted an unprecedented number of resurgent and “new” infectious diseases on a global scale, with antibiotic resistance being among the new diseases represents one of the most serious threats to human health, and a serious threat to the treatment of infectious diseases.²

Ramifications Of Antibiotic Resistance
The overuse of antibiotics contributes to the emergence of antibiotic-resistant infections (ARIs) that are costly and difficult to treat.^3,4 Ongoing and consistent use of antibiotics allows microbes the opportunity to evolve, enabling them to efficiently adapt to new environments. A single dose of antibiotics leads to a greater risk of resistant organisms to that antibiotic in the person for up to a year.⁵ Drug-resistant “superbug” infections, such as Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficle, are a significant cause of mortality. In 2005, more than 95,000 people in the U.S. developed severe MRSA infections, which led to 9,000 deaths.^6,7 In the U.S., ARIs are responsible for $20 billion in excess health care costs, $35 billion in societal costs and $8 million in additional hospital days. Reducing ARIs by just 20 percent would save $3.2 to $5.2 billion in health care costs each year and eliminate up to $11.3 million in additional in-hospital days for patients with ARIs.⁸ Even mainstream media has recognized the problem.

According to a report by CBS News:
Antibiotic overuse has led to the growth of drug-resistant strains of bacteria. Each year 90,000 Americans die from health care-associated infections, many of which are drugresistant. And, the number is growing. From 1993 to 2005 the number of hospital stays involving Methicillin-resistant Staphylococcus aureus (MRSA)—bacteria that causes severe infections such as bloodstream infections, surgical site infections, or pneumonia—went up from 1,900 to 368,000 in the U.S. alone. Deaths due to Clostridium difficle—bacteria commonly known as C. diff that causes several diarrhea and intestinal problems—went up 35 percent each year from 1999 to 2004.⁹

Reasons For Antibiotic Overuse
So why are antibiotics overused in the first instance? The answer is four-pronged. First, determining if an infection is viral or bacterial is expensive and time-consuming and concerns over malpractice lead many physicians to over-prescribe antibiotics.^10,11 Second, some patients pressure providers to prescribe antibiotics for conditions for which they are inappropriate, such as the common cold or sore throat, or inappropriately save antibiotics for later use, both of which can lead to increased antibiotic resistance.^12,13 Third, approximately 70 percent of antibiotics used in the U.S. are used in the non-therapeutic (prophylactic) treatment of livestock cattle, swine, and poultry, and although the FDA issued voluntary guidelines in 2010 urging farmers not to use antibiotics for livestock growth, the guidelines are not yet mandatory.^14,15 Fourth, evidence-based research on appropriate and inappropriate antibiotic use is often lacking in the medical community.¹⁶ A fifth reason may be public ignorance.

An Unfortunate Case Of Ignorance
Part of the growing problem of antibiotic resistance in the United States may be attributed to the fact that many Americans don’t know what the drugs should be used for and what they can actually do. The Pew Charitable Trusts in conjunction with the Centers for Disease Control and Prevention (CDC) surveyed 1,004 adults about their understanding about the use of antibiotics. In addition, they asked focus groups of frequent antibiotic users as well as a cross section of adults about their antibiotic-use beliefs and habits. Only 44 percent of surveyed Americans recognized as somewhat or a big problem that some diseases are becoming resistant to antibiotics. While 90 percent of Americans recognize that antibiotics can fight bacterial infections like strep throat, more than one-third falsely believe that they are also effective at fighting viral infections like the common cold. Furthermore, only 47 percent of Americans realize that their overuse of prescription antibiotics can harm others beside themselves.¹⁷

What Is The Goal?
In considering herbal alternatives to antibiotics, it is important to examine the intended goal in using the specific herbal medicine. Is the purpose of the herb to 1) stimulate and promote your body’s own healthy immune response, 2) directly do battle with bacteria, or 3) both? From my perspective as a credentialed herbalist and nutritionist, it is important to do both. First and foremost, you should always strive to make your immune system as healthy and functional as possible. This way, when unwanted bacteria and viruses do invade, your immune system will be in a good position to fit back. Following is a discussion of a few key herbs (and a few other dietary supplements) that can help you achieve these goals. Please keep in mind that given the space limitations of this article, it will not be possible to address all immune/antibacterial herbs. However, for a comprehensive treatise on the topic, I recommend Herbal Antibiotics: Natural Alternatives for Treating Drug-Resistant Bacteria, by Stephen Harrod Buhner.

Diet And The Immune System
Before jumping into the herbs, I just want to say a couple of words about your diet. It is important to restrict sugar since sugar interferes with the ability of white blood cells to destroy bacteria. I’m not talking about the type or amount of sugar you get from eating fruit, but rather the amount you get from drinking soda and eating sweets and other junk food. Likewise, alcohol interferes with a wide variety of immune defenses, and excessive dietary fat reduces natural killer cell activity. So just eating a healthy diet can be beneficial for good immune function.¹⁸ Now, onto the herbs.

Echinacea
Arguably, Echinacea is the granddaddy of all immune-enhancing herbs. Best known for its use in the treatment of the common cold, there are three species of Echinacea commonly used in herbal medicine: Echinacea purpurea, E. angustifolia, and E. pallida (of these, the first two are most popular). The aerial (above ground) parts of the herb and the root contain the medicinal components, including phenolics, caffeic acid esters (e.g., echinacosides), flavonoids, alkylamides, volatile oils, polysaccharides, polyacetylenes.¹⁹

Echinacea is an immune stimulant/supporter. It is excellent in helping to prevent and treat colds and influenza. Research reveals that Echinacea supports the immune system by activating white blood cells (lymphocytes and macrophages).²⁰ Echinacea also increases the production of interferon, an immune component that is important in responding to viral infections.²¹

Several double-blind, clinical studies have confirmed Echinacea’s effectiveness in treating colds and flu.^22,23,24,25 However, some research suggests that Echinacea may be more effective if used at the onset of these conditions.^26,27 One study involving 238 subjects confirmed that Echinacea was safe and effective in producing a rapid improvement of cold symptoms. In the subgroup of patients who started therapy at an early phase of their cold, the effectiveness of Echinacea was most prominent.²⁸ In a similar study, 246 subjects with a cold were treated with Echinacea preparations or a placebo. Those treated with the Echinacea preparations experienced a reduction of symptoms, significantly more effective than the placebo. The researchers concluded that the Echinacea preparations “represent a low risk and effective alternative to the standard symptomatic medicines in the acute treatment of common cold.”²⁹

In a meta-analysis of 14 studies³⁰, researchers found that taking Echinacea cut the risk of catching the common cold by 58 percent, and if subjects already had a cold it decreased the duration by 1.4 days. In one of the studies, Echinacea taken in combination with vitamin C reduced cold incidence by 86 percent, and when the herbal was used alone the incidence of cold was reduced by 65 percent. The bottom line is that when used appropriately, Echinacea is effective in preventing and treating the common cold.

NOTE: A much-publicized study from the July 28, 2005 issue of the New England Journal of Medicine concluded that Echinacea did not have a significant effect on infection with a rhinovirus (one of the 200 viruses that can cause the common cold), but the methodology has been strongly questioned by herbal experts. One such error in methodology is the fact that the study did not use a commercially available product, and dosage was lower than the dose typically used in research and common practice.

Besides colds and flu, Germany’s Commission E Monographs (an internationally authoritative source of credible information on the use of herbs for various disorders) indicates that among Echinacea’s uses, this herb can be used to treat chronic infections of the respiratory tract.³¹ Other current and evidence based uses of Echinacea include, but are not limited to: Vaginal candidiasis, ear, urinary and sinus infections, allergies, herpes, cystitis, bronchitis, prostatitis, tonsillitis, and laryngitis.³²

A good dosage range for Echinacea extract is 200–300 mg, jumping up to 900–1200 mg daily (in 3–5 divided doses) for acute infection (e.g. cold or flu).³³ While some sources have suggested that Echinacea should not be used with drugs intended to suppress the immune system, such suggestions are speculative and lack clinical documentation.³⁴

At this point is should also be noted there is a popular misconception that Echinacea should only be used for a limited period of time, since it will cease its effectiveness otherwise. This misconception was based upon misinterpretations of a specific study on Echinacea, which demonstrated decreased immune activity after about 10 days.³⁵ However, if the study is carefully read, it is clear that the Echinacea was only administered for five days; after which point it was discontinued. Only when it was discontinued did immune activity begin to decline; and even then it still remained elevated above normal for a few days.³⁶ Furthermore, other research (as well as a history of traditional use) support the effectiveness of Echinacea when used for extended periods of time.¹¹

Andrographis and Eleutherococcus senticosus
Andrographis paniculata has a history of use in both Ayurvedic and traditional Chinese medicine.³⁷ It contains a number of bitter constituents, which appear to have both immune-stimulating and anti-inflammatory activity.³⁸ Double-blind studies have found that Andrographis may help reduce the severity of symptoms in individuals suffering from the common cold.^39,40,41,42

In the very recent past, Eleutherococcus senticosus, or Eleuthero for short, was commonly called “Siberian Ginseng.” This name was botanically incorrect since Eleuthero is not even in the same genus (plant family) as Panax ginseng. Nevertheless, like Panax species, Eleuthero shows excellent adaptogenic activity (an adaptogen is an agent that helps the body adapt to stress). Russian explorers, divers, sailors, and miners also used Eleuthero to prevent stress-related illness.⁴³ In addition, evidence also suggests that Eleuthero may prove valuable in the long-term management of various diseases of the immune system, including HIV infection and chronic fatigue syndrome.⁴⁴ In Chinese medicine, it was used to prevent respiratory tract infections, colds and flu.

Of particular interest is using a combination of Andrographis and Eleuthero to treat upper respiratory infections. In two randomized, parallel-group clinical studies⁴⁵, patients diagnosed with influenza (540 patients and 66 patients, respectively) were treated with a combination of Andrographis and Eleuthero, or nothing at all (in the control group). In both studies, the differences in the duration of sick leave (7.2 days versus 9.8 days in the control group) and frequency of post-influenza complications indicated that the Andrographis/Eleuthero combination contributed to quicker recovery and reduced the risk of post-influenza complications. The results showed that in Andrographis/Eleuthero-treated patients the symptoms had become less pronounced and the temperature had returned more rapidly to normal values, and symptoms such as headache, muscle pain, and conjunctivitis disappeared sooner than in patients of the control group.

In addition, two randomized double-blind, placebo-controlled parallel group clinical trials⁴⁶ were performed to investigate the effect of an Andrographis/Eleuthero combination in the treatment of uncomplicated upper-respiratory tract infections. This includes common cold, rhinitis, nasopharyngitis (Inflammation of the nasal passages and of upper sore throat) and pharyngitis (sore throat). There were 46 patients in one study, and 179 patients in another. In both studies, the total symptom score and total diagnosis score showed highly significant improvement in the Andrographis/ Eleuthero group as compared with the placebo. Throat symptoms/signs, were found to show the most significant improvement. There was a 55 percent better improvement in the symptom score for the treatment group as compared with the placebo group.

Also, a double-blind, placebo-controlled, parallel-group clinical study⁴⁷ was carried out to evaluate the effect of an Andrographis/Eleuthero combination in the treatment of acute upper respiratory tract infections, including sinusitis. Ninetyfive individuals in the treatment group and 90 individuals in the placebo group completed the study according to the protocol. Temperature, headache, muscle aches, throat symptoms, cough, nasal symptoms, general malaise and eye symptoms were taken as outcome measures with given scores. The total score analysis showed a highly significant improvement in the Andrographis/Eleuthero combination group versus the placebo. The individual symptoms of headache and nasal and throat symptoms together with general malaise showed the most significant improvement while cough and eye symptoms did not differ significantly between the groups. Temperature was moderately reduced in the Andrographis/Eleuthero combination group. The authors of the study concluded that the Andrographis/Eleuthero combination had a positive effect in the treatment of acute upper respiratory tract infections and also relieved the inflammatory symptoms of sinusitis.

Doses of Andrographis/Eleuthero should be in the range of in the range of 340 mg Andrographis paniculata extract (providing 21 mg andrographolide and deoxyandrographolide), 39 mg Eleuthero extract (providing 2 percent total Eleutheroside B and Eleutheroside E).

Berberine
Berberine is a bitter-tasting, yellow, plant alkaloid found in the roots of various herbs, including goldenseal (Hydrastis canadensis), barberry (Berberis vulgaris), Oregon grape (Berberis aquifolium), goldthread (Coptis chinensis) and tree turmeric (Berberis aristata). This compound has a long history of medicinal use in Chinese and Ayurvedic medicine. Berberine containing plants may help promote immune response by increasing the production of antigen specific immunoglobulins,⁴⁸ and may also have a direct effect against bacteria.^49,50 For example, berberine may help fight urinary tract infections since it inhibits bacteria from adhering to the wall of the urinary bladder.⁵¹ One possible mechanism by which this takes place is that berberine might inhibit bacterial sortase, a protein responsible for anchoring bacteria to cell membranes.⁵² Berberine was also shown to be effective in an integrative treatment against patients with chloroquine-resistant malaria⁵³ and bacterial-induced diarrhea.⁵⁴

In addition, berberine has activity against Candida yeast.⁵⁵ In fact, berberine was demonstrated to be effective in reducing the growth of the invasive mycelial form of Candida albicans.⁵⁶ In addition, extracellular enzymes secreted by Candida albicans are considered to be responsible for penetration of the yeast into host cells, and general overgrowth. Berberine has been shown to reduce these enzymes and the consequent adherence of Candida to epithelial cells. Furthermore, berberine was able to suppress symptoms of Candida overgrowth and accelerated elimination of the yeast.⁵⁷

Regardless of the herbal source, try to get 400 mg berberine daily.

Shiitake and AHCC
For thousands of years, mushrooms have been used as both food and medicine in various cultures. One of those mushrooms, Shiitake (Lentinula edodes)⁵⁸, is currently used for promoting healthy immune function⁵⁹, healthy liver function⁶⁰ and modulating the unwanted growth of mutated stomach⁶¹ and pancreas cells⁶², and has been validated in scientific literature for these purposes.

Active Hexose Correlated Compound (AHCC) is an extract derived from Shiitake, as well as other species of Basidiomycete family of mushrooms. AHCC is a mixture of polysaccharides, amino acids, lipids, and minerals. Oligosaccharides make up about 74 percent of AHCC.⁶³ Like its predecessor, AHCC has antioxidant effects, and is thought to act as a biological response modifier. It seems to promote the activity of natural killer (NK) cells in patients with unwanted growth of mutated cells. In animal models, it also seems to protect against carbon tetrachloride-induced liver damage, promote healthy blood glucose levels within a normal range, and decrease apoptosis (i.e., programmed cell death) of the thymus.⁶⁴

AHCC demonstrated early clinical promise in promoting healthy immune response. This was shown in animal research where AHCC helped restore immune response that had been negatively affected by trauma, infection, and food deprivation.⁶⁶ In humans, the effect of AHCC on immune response was investigated by measuring the number and function of circulating dendritic cells (DCs), a type of immune cell, in healthy volunteers. Twenty-one healthy volunteers were randomized to receive placebo or AHCC for four weeks. The results were that the AHCC group had a significantly higher number of total DCs compared to when they first started the study, and compared to the control subjects. Other types of immune cells were also significantly increased in the AHCC group compared to controls.⁶⁷

The effects of AHCC in a clinical setting were examined in patients who had surgery for the undesirable growth of mutated liver cells. A total of 269 patients participated in the study, with 113 receiving AHCC. The results were that the AHCC group had a significantly longer period of no recurrence of mutated liver cells, and an increased overall survival rate when compared to the control group.⁶⁸

A prospective cohort study was performed with 44 patients with undesirable growth of mutated liver cells. All of the patients underwent supportive care. Survival time, quality of life, clinical and immunological parameters related to liver function, cellular immunity, and patient status were determined. Of the 44 patients, 34 and 10 received AHCC and placebo (control) orally, respectively. Patients in the AHCC treated-group had a significantly prolonged survival when compared to the control group, and quality of life in terms of mental stability, general physical health status, and ability to have normal activities were significantly improved after three months of AHCC treatment.

An effective daily dose is 3–6 grams AHCC daily.

Pomegranates
Pomegranates are high in polyphenolic compounds, making its juice higher in antioxidant activity than red wine and green tea.⁷⁰ The most abundant of these compounds is ellagic acid, which has been shown in research to be the antioxidant responsible for the free-radical scavenging ability of pomegranate juice.⁷¹ According to some researchers⁷², the actions of pomegranate’s components suggest a wide range of clinical applications for the treatment and prevention of cancer, as well as other diseases where chronic inflammation is believed to play an essential developmental role, suggesting immune modulatory activity. Of particular interest where ARIs are concerned, one study⁷³ found that pomegranate had specific antibacterial activity against MRSA. The authors of that study suggest a beneficial effect from the daily intake of pomegranate “as dietary supplements to augment the human immune system’s antioxidant, antimalarial and antimicrobial capacities.”

The consumption of 2–8 ounces of pomegranate juice is a good daily dose.

Other Dietary Supplements For General Immune Response
In terms of dietary supplements, there are some general immune-promoting nutrients, which may have benefit promoting immune response:

• Vitamin A—Plays an important role in immune system function and helps mucous membranes, including those in the lungs, resist invasion by microorganisms.⁷⁴ Daily dose: 5,000-10,000 IU.
• Vitamin C—Stimulates the immune system by both elevating interferon levels and enhancing the activity of certain immune cells.⁷⁵ Daily dose: 500-1000 mg. Increase to 1000 mg every other waking hour during acute infection.
• Zinc—Marginal deficiencies result in impairments of immune function.⁷⁶ Supplementation with zinc has been shown to increase immune function in healthy people.⁷⁷ Daily dose: 15 mg. Increase to 15 mg, three times daily in lozenge form during acute infection.
• Probiotics—Probiotics are well established for their role in immune health, and have been shown to have efficacy in the treatment of bacterial vaginosis^78,79 and irritable bowel syndrome.⁸⁰ Daily dose: 5–10 billion CFU of Lactobacillus and/or Bifidobacteria species.

Conclusion
In addition to those listed, there are many other herbs with value to the immune system and/or with antibacterial properties. These include Astragalus membranaceus, Picrorrhiza kurroa, Thuja occidentalis and Green tea, just to name a few. If it wasn’t included in this article, don’t assume it doesn’t have value. The fact is, it most likely does but I could only choose a few to discuss here. In any case, use of the herbs and other supplements discussed in this article may help you support and maintain a healthy immune system, which is your best defense against any bacteria and viruses. Likewise, some of these herbs may also have direct effects against specific microorganisms. Nevertheless, if you are sick you should see your doctor to have your individual situation assessed.

Link to References