Increased lifespan is now a given in modern societies. Increasing the healthspan is the next challenge as degenerative diseases of ageing take increasing numbers of people. Jack Challem investigates the foremost science-backed ingredients

Over the past 100 years, millions of people have benefited from substantial increases in life expectancy, the combined result of improved sanitation, hygiene and medical care. Yet these phenomenal increases in longevity have been accompanied by an unprecedented rise in age-related degenerative diseases, including heart disease, cancer, diabetes and Alzheimer's disease.

As people live longer, their genes suffer greater numbers of mutations, resulting in a deterioration of genetic instructions. At the same time, biochemical pathways become less functional, leading to reduced cell function and a greater risk of disease.

One way of reconciling this catch-22 of ageing is to preserve, as best as possible, the biochemical activities characteristic of younger people. It's more than a pipe dream. Research supports the argument that good nutrition and dietary supplements can help slow and reverse age-related physical and mental declines. The scientific rationale is sound and straightforward: nutrients provide the chemical substrates of biochemistry, and nutritional supplements can shore up weak biochemical pathways.

Along these lines, we focus on four age-related health issues — inflammation, hyperglycaemia, osteoarthritis and cognitive decline — and nutritional ingredients that show promise in preventing and reversing them.

Inflammation
In recent years, the medical recognition of inflammation has moved beyond arthritis and other '-itis' diseases. Although the body's inflammatory response protects against infection, chronic inflammation is an undercurrent in every disease process. For example, inflammation plays a major role in the development of heart disease, cancer and Alzheimer's disease. In addition, chronic low-grade inflammation increases with age.

Antioxidants: Oxidation — often considered the uncontrolled generation of free radicals — stimulates inflammation and, conversely, antioxidants can help quell inflammation. Natural-source vitamin E reduces levels of C-reactive protein, a key marker of chronic low-grade inflammation.1^,2^,3 Other antioxidants, including vitamin C, appear to have similar benefits.4 Polyphenols, including flavonoids, may be among the most potent anti-inflammatory compounds; they are especially concentrated in herbal extracts.

Curcumin: More than 2,000 scientific papers have been published on curcumin, a polyphenol and the active constituent of the spice turmeric. Curcumin is a powerful broad-spectrum anti-inflammatory — it acts on almost 100 promoters of inflammation, including nuclear factor kappa beta (NFkB, a gene-transcription factor), interleukin-6 (a cytokine), and cyclooxygenase-2 (COX-2, a pro-inflammatory enzyme).5 Clinically, curcumin has been used to treat a growing number of conditions with strong inflammatory components, including rheumatoid arthritis, psoriasis and irritable bowel syndrome.6

Pycnogenol: This extract of French maritime pine trees is a rich trove of antioxidants and anti-inflammatory polyphenols. It blunts the activity of inflammation-promoting COX-1 and COX-2 enzymes.7 In a recent study, Pycnogenol supplements reduced pain and stiffness in people with osteoarthritis.⁸ In another study, this one focusing on asthma, children taking Pycnogenol gained better lung function, and many were able to reduce or stop using their medications.9

Astaxanthin: This carotenoid has impressive anti-inflammatory properties and appears to protect against heart damage.10 Astaxanthin works at least in part by inhibiting NFkB, which stimulates the expression of inflammation-promoting genes.¹¹ Because astaxanthin influences gene expression, it likely has broad spectrum anti-inflammatory properties.

Omega-3 fish oils: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two principal omega-3 polyunsaturated fats (PUFAs) found in fish oils, have significant anti-inflammatory properties. The omega-3s increase the activity of prostaglandin E1, which helps suppress pro-inflammatory prostaglandin E2. Omega-3 supplements can balance Western diets that tend to be high in corn, safflower, peanut and soybean oils, all of which are high in the pro-inflammatory omega-6 PUFAs.

Gamma-linolenic acid: Although gamma-linolenic acid (GLA) is an omega-6 PUFA, it has significant anti-inflammatory properties and is also synergistic with the omega-3s. GLA may be particularly beneficial because trans fats, a constituent of many processed foods, inhibit delta-6-desaturase, the enzyme that converts linoleic acid to GLA. GLA supplements appear to bypass or correct this biochemical bottleneck. Studies have found GLA supplements helpful in reducing inflammation stemming from athletic injuries and rheumatoid arthritis.12^,13

Blood sugar
Elevated blood sugar and insulin resistance are the hallmarks of prediabetes and full-blown diabetes mellitus. Hyperglycaemia is strongly linked to accelerated ageing, and blood-sugar levels tend to increase with age. Upwards of 100 million Americans currently have prediabetes, and 20 million have type 2 diabetes. Experts predict a 32 per cent increase in the incidence of diabetes in Europe by 2030. Diabetes will also increase by 164 per cent in the Middle East, 150 per cent in India, and 148 per cent in South America.14

Resveratrol: Resveratrol, found in red wine, can increase the activity of SIRT1, a principal anti-ageing gene and one that also regulates insulin sensitivity.15 In studies, mice given resveratrol maintained normal liver function and had relatively low levels of glucose, insulin and insulinlike growth factor-1.16 The average lifespan of the mice increased by about 15 per cent, which may be related to both changes in gene function and lower levels of glucose and insulin.¹⁷

Vitamin D: A large clinical study of women found that women who took supplements containing 800IU of vitamin D and 1,200mg calcium daily had a 33 per cent lower risk of developing diabetes over 20 years.18 Both nutrients are needed for normal insulin function.19 A recent epidemiological study reported that people with the highest blood levels of vitamin D were 40 per cent less likely to develop type 2 diabetes.20

Silymarin: Two clinical studies have found that this extract of milk thistle (Silybum marianum) can significantly improve many of the clinical signs of diabetes, including fasting blood sugar, insulin, glycated hemoglobin (HbA1c), and blood lipids. 21^,22 The dosage in these studies was 200mg three times daily, which could likely be reduced if the herb were combined with other ingredients.

Chromium: Niacin-bound chromium polynicotinate and chromium picolinate can significantly reduce blood sugar and insulin levels.23 In one study, large doses (1,000mcg) of chromium picolinate led to substantial decreases in blood-sugar and insulin levels after just four months.24 In another trial, supplements of niacin-bound chromium significantly decreased fasting blood sugar, with modest reductions in triglyceride and glycated hemoglobin (HbA1c) after three months.^25,26

Alpha lipoic and R-lipoic acids: Alpha lipoic acid has long been used in Germany as a medication to treat diabetes-related nerve problems. It functions as an antioxidant and cofactor in the Krebs cycle, and it improves insulin function and sensitivity.27^,28^,29 The biologically active isomer is the R form, which constitutes half of alpha lipoic acid.30 R-lipoic acid is available as an ingredient, although it is more expensive than alpha lipoic acid.

Vitamin K: Vitamin K is needed for the synthesis of osteocalcin, long recognised as a bone-matrix protein. In 2007, researchers reported in the journal Cell that osteocalcin also functions as a metabolic hormone regulating pancreatic beta-cell activity, insulin, glucose and the size of fat cells.31 Although this was an animal study, its publication in a prestigious journal is likely to stimulate further research on vitamin K, osteocalcin and glucose tolerance. Vitamin K2 is the most biologically active form.

Osteoarthritis
Osteoarthritis is characterised by inflamed joints and the breakdown of chondrocytes, the cells that form articular cartilage. Cartilage is a highly complex tissue consisting of several types of collagen proteins (eg, type 2 collagen) and noncollagen proteins (eg, proteoglycans). Aggrecan, the principal type of proteoglycan, provides compressibility; it consists of chondroitin sulfate, hyaluronic acids, and other substances. Many of the building blocks of cartilage reduce joint pain, and some can retard or reverse the actual breakdown of cartilage.

Thiols: In common usage, thiols refer to sulfur-containing nutrients. Sulfur-containing compounds are key constituents of collagen, cartilage and many other proteins in the body. In particular, methylsulfonylmethane (MSM), glucosamine sulfate, chrondoitin sulfate, and S-adenosylmethionine (SAMe) are sulfur-containing ingredients that have been found helpful in osteoarthritis.

In a recent study, patients with knee osteoarthritis took 3g MSM twice daily for 12 weeks. The supplement significantly reduced pain and improved physical mobility.32 Patients in a separate study also had substantial reductions in knee pain after taking 1,500mg MSM daily, gaining still greater benefits after combining MSM and glucosamine sulfate.33

In addition to its analgesic properties, glucosamine sulfate stimulates the growth of cartilage.34 Researchers recently followed up on patients who had taken either glucosamine sulfate or placebos for one year. People who had taken glucosamine sulfate were half as likely to undergo total knee-replacement surgery over the subsequent eight years.35 Research also supports the use of chondroitin sulfate in reducing knee pain and maintaining knee cartilage.36 Likewise, S-adenosylmethionine (SAMe) may be as effective as ibuprofen in reducing osteoarthritis pain.^37,38

Avocado/soybean unsaponifiables (ASU): The unusual name refers to specific lipid extracts of avocado and soybean that cannot be used to make soap. ASUs have been found to reduce pain, slow the breakdown of existing cartilage and stimulate the production of new cartilage.39^,40^,41 They work in part by reducing the activity of inflammatory cytokines.42

Hyaluronan: Injections of hyaluronan (also known as hyaluronic acid) into joints have proved to be an effective, though expensive, treatment of pain from knee osteoarthritis.43 Hyaluronan increases the viscosity of joint fluid, which helps lubricate and cushion joints. The injections use large molecular-weight hyaluronan, which is not absorbed orally. However, low molecular-weight hyaluronan appears to be well absorbed, according to preliminary animal studies.⁴⁴

Type 2 collagen: More than 90 per cent of the collagen in cartilage consists of type 2 collagen. In recent years, numerous studies have found that type 2 collagen, obtained from chicken or bovine sources, stimulates the synthesis of chondrocytes.45

Omega-3 fatty acids: Aggrecan, the principal noncollagen protein in cartilage, is broken down by a family of enzymes known as aggrecanases. Cell studies have found that omega-3 fatty acids can inhibit the activity of aggrecanases.46 In one experiment, researchers cultured cells from the knees of osteoarthritis patients and observed that inflammation yields large amounts of COX-2 and led to the continued breakdown of the cells. Adding omega-3 fatty acids to the cell medium reduced COX-2 activity and prevented the breakdown of cells.47

Cognitive decline
An estimated 18 million people worldwide currently have Alzheimer's disease or other types of dementia, including 4.5 million Americans and 775,000 Britons. The worldwide incidence may reach 34 million by the year 2025, according to the London-based Alzheimer's Disease International organisation.48 Even without Alzheimer's disease, age-related cognitive decline reduces human functionality and productivity.

Omega-3 fatty acids: Many studies have found a strong association between high fish intake or high blood levels of the omega-3 fatty acids and a slower rate of cognitive decline among the elderly. In a clinical trial, researchers at the Karolinska Institute, Sweden, gave omega-3 fish oils (1.7g DHA and 0.6g EPA) to 174 men and women with Alzheimer's disease. Patients suffering from mild (but not severe) cognitive impairment improved during six months of supplementation.49

Beta-carotene: As antioxidants, carotenoids may slow age-related cognitive decline. In a recent study, published in Archives of Internal Medicine, Harvard University researchers followed up on 4,000 men who had taken either beta-carotene supplements (50mg, equivalent to 83,333IU) or placebos every other day for an average of 18 years. Men who had been taking beta-carotene scored significantly higher on several cognitive tests, compared with those who had been taking placebos.50

Vitamin B12: Approximately one third of seniors suffer from atrophic gastritis, a condition that interferes with vitamin B12 absorption. Many studies have found that vitamin B12 deficiency can mimic Alzheimer's disease and other types of dementia. In these cases, replenishing vitamin B12 often restores normal cognitive function. 51^,52^,53^,54 Other B-complex vitamins, including niacin and folic acid, are likely helpful in combination with vitamin B12.

Phosphatidylserine: Phosphatidylserine is incorporated into the fatty membranes (walls) of brain cells, where they maintain a youthful flexibility and enable communication between brain cells. Phosphatidylserine has also been shown to improve memory and to reverse age-related memory loss. Researchers gave 300mg phosphatidylserine daily to 149 patients with age-related memory impairment. After 12 weeks, patients taking phosphatidylserine scored about 30 per cent better in terms of learning and recalling names, faces and numbers compared with people taking placebos.55 Other clinical trials have reported similar benefits.56

Curcumin: People who regularly consume curry, rich in turmeric and curcumin, are about one half as likely to develop age-related cognitive problems, compared with people who rarely eat curry.57 The role of curcumin has been confirmed in cell studies, which have found that it enhances the ability of white blood cells to scavenge for amyloid-beta-amyloid plaque, one of the hallmarks of Alzheimer's disease.⁵⁸

The multidimensional approach
Because nutrients function as part of a biochemical network, formulas containing multiple ingredients are likely to provide greater health benefits than any single ingredient. Product formulators would do well focusing on ingredients that have complementary or synergistic properties.

Jack Challem is the author of The Food-Mood Solution, and Stop Prediabetes Now, published by John Wiley & Sons.

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