Longevity for the 99%

4 supplements for improving healthspan without breaking the bank

Somedays it seems that all of the people making headlines in the longevity field are millionaires. Or billionaires. Longevity and healthspan are not just for the wealthy. Everyone can benefit from the latest scientific research, and it doesn't have to cost millions.

Let’s take a look at some of the inexpensive interventions that can prevent the diseases of aging without breaking the bank - or risking negative side effects.

I'm not going to talk about free exercise, healthy food choices, and getting outside in the sunshine. You all know that stuff!

Instead, I'm going to focus on relatively inexpensive interventions that seem to give you the biggest bang for your buck.

This is not medical advice, and I’m not a doctor! I’m just reading the research studies and explaining them. Talk with your own doctor if you have questions before starting anything new.

Creatine:

Creatine is an inexpensive supplement that has been used by bodybuilders for decades. But the research on creatine goes far beyond improving the physique of bodybuilders. Creatine is used in high energy demand situations in the muscle and brain to convert ADP to ATP.

Creatine for heart health:
A randomized controlled trial (RCT) in older adults looked at the effect of 20g/day of creatine for 7 days. The results showed positive benefits on vascular parameters including improved arterial stiffness and atherosclerosis markers.[ref] Notably, the benefits were seen in just one week.

Creatine for the methylation cycle, homocysteine:
The methylation cycle produces methyl groups (one carbon plus three hydrogens) that are used in many different processes in the body. It does this through a process that involves methionine and homocysteine. Without enough of the inputs needed to make methyl groups, homocysteine levels can rise. High homocysteine levels can lead to oxidative stress in the blood vessels and is a risk factor for cardiovascular disease. (Read more on homocysteine here)

About 40% of the methyl groups are used to synthesize creatine. Supplementing with creatine takes the strain off the methylation cycle and homocysteine levels drop.

An RCT involving healthy adults engaged in resistance training showed that creatine supplementation over eight weeks reduced homocysteine levels. The study used an initial dose of 25 g/d of creatine for the first five days, followed by 5 g/day for the rest of the trial.[ref]

Creatine for cognitive health:
Creatine is critical in brain function, and genetic mutations that reduce creatine transport to the brain have devastating effects from infancy. That said - creatine isn’t going to give you Limitless brain power if you have a healthy brain to begin with. The effects of creatine for improving cognitive health in aging seem to be more significantly noticeable in people who have some mild issues with memory or who feel like they aren’t as sharp anymore. It also is likely of benefit for people who aren’t getting quite enough oxygen to the brain. This is a great overview of the studies on creatine for brain bioenergetics.

Dosing, side effects: Most studies on creatine use 20g/day for 5-7 days and then drop to 5g/day. Safety studies generally show that it is safe, but I would strongly suggest talking with your doctor about creatine (and any supplement) if you have chronic kidney disease.

The main side effect is that some people find that creatine makes them puffy or bloated feeling from retaining more water. Creatine moves into cells using the SLC6A8 transporter (also called CT1), which is a sodium- and chloride-dependent transporter. If you are having trouble with retaining water on creatine, look at how much sodium and potassium you are getting. While creatine needs sodium to move into the cells, the body is very good at controlling potassium/sodium balance, so if you are low on either, it could mean that creatine is not getting into the cells and causing water retention.

DHA and EPA for SPM production:

The resolution of inflammation is an active process that utilizes specialized pro-resolving mediators (SPMs) synthesized from DHA and EPA.

Without sufficient DHA and EPA, inflammation lingers and causes cell damage. Excess inflammation and cell damage are at the heart of everything that goes wrong with aging.

All of that I can say with no hesitancy. The trickier part is how to increase DHA and EPA levels…

Studies using low-dose fish oil usually show little effect, and it isn’t a cure-all. Thus, the headlines about fish oil are usually pretty ambiguous. For example, studies show that it doesn’t improve insulin sensitivity in people with metabolic disorders, and it doesn’t cure AFib.[ref] One meta-analysis showed that fish oil reduced cardiovascular events by 15%, but then concluded “these results do not justify adding fish oils systematically to the heavy pharmaceutical assortment already recommended in CHD patients.”

Part of the problem with clinical trials using DHA and EPA supplements is that they are often using either low doses or low-quality products. Taking oxidized, rancid fish oil pills is not going to promote health. So the key is to find a high-quality DHA and EPA supplement that is consistently good. Or… to eat more fatty fish (that aren’t full of mercury and microplastics.)

How much? Studies on increasing the production of specialized pro-resolving mediators (the SPMs that resolve inflammation) show that around 4g/day of DHA/EPA may be needed for people with chronic diseases.[ref]

ConsumerLab.com tests supplements off the shelf. Of the brands tested, a couple were shown to be oxidized: Jamieson Omega-3 and Wiley’s Finest Wild Alaskan. The CL top pick for high-dose marine oil was Carlson Maximum Omega 2,000* and Kirkland brand (Costco) for low dose. All of the tested marine oils passed the heavy metals tests.

Algae oil and krill oil are other sources of DHA and EPA, and they have the advantage of being less likely to be oxidized. More likely to be oxidized, according to a study of 72 omega-3 supplements, are flavored supplements - 68% of them were rancid, compared to only 13% of unflavored supplements.[ref]

Some companies are selling specific SPM supplements, which contain fractionated marine oil that is used for synthesizing specialized pro-resolving mediators. They may be a great option, but they don’t really quality as inexpensive… This SPM supplement from Designs for Health is $53.

My workaround - I’m increasing my fish consumption (local, wild-caught trout), eating eggs that have DHA and EPA added to the chicken feed, and then supplementing several days a week with high-dose fish oil. I’ve tried expensive SPMs and several different brands of fish oil. My theory - which honestly may be wrong - is that if I switch things up every month or two, then I minimize the odds of continually getting something that is a negative (e.g. mercury, oxidized fish oil, microplastics, toxicants).

Fighting inflammation:

Chronic inflammation causes oxidative stress in the cell, which can lead to DNA damage, cell damage, and mitochondrial dysfunction — all of which are at the heart of age-related diseases.

Here are three relatively inexpensive supplements with solid research for modulating different pathways of inflammation:

• Curcumin

• Hesperidin

• Quercetin

I’ll go into a bit of the research on each, but I do want to caution that you should talk with your doctor if you are on any prescription meds before taking any of these. Also - if you have slow COMT function, quercetin and curcumin may cause irritability, especially if combined with methyl donor supplements.

Curcumin:
Studies show that curcumin reduces inflammation in a couple of ways. A randomized clinical trial of curcumin (1g/day) in people with metabolic syndrome showed statistically significant reductions in TNF-α, IL-6, TGF-β, and MCP-1.[ref] Another study showed that curcumin reduces IL-17 production through the induction of IDO (tryptophan enzyme in the kynurenine pathway).[ref]

Clinical trial highlights:

• Curcumin supplementation improved cognitive performance in middle-aged, overweight people.[ref]

• Curcumin supplementation increased handgrip strength and weight lifting strength compared to placebo.[ref]

• A curcumin-phosphatidylcholine complex (Meriva) was effective in decreasing inflammatory markers and in decreasing joint pain.[ref]

Here’s a curcumin supplement that I like and take periodically (at 500 mg/day).

Hesperidin:
Hesperidin is a flavonoid found in citrus fruits. Studies show that it acts as an anti-inflammatory by reducing TNF-alpha, IL-6, and CRP levels.[ref][ref][ref] In addition, studies show that hesperidin can act as a mast cell degranulation inhibitor by acting on HIF-1A.[ref]

Clinical trial highlights:

• Another clinical trial using 1g/day of hesperidin also showed decreased triglycerides and lower blood pressure.[ref]

• A 12-week trial of hesperidin in orange juice showed that it decreased blood pressure and also downregulated proinflammatory genes.[ref]

• Hesperidin supplements (500 mg, 2x a day) reduced fasting glucose, blood pressure, triglycerides, and TNF-α in a placebo-controlled trial on people with metabolic syndrome.[ref]

Quercetin:
Quercetin is a natural flavonoid that acts both as an antioxidant and anti-inflammatory. It’s a free radical scavenger shown in studies to help prevent oxidized cholesterol, and RCTs show that it also helps reduce the concentration of oxidized LDL.[ref][ref]

Clinical trial highlights:

• A randomized, double-blind, placebo-controlled crossover trial found that 160 mg/d of quercetin reduced methylglyoxal, a precursor for advanced glycation end products, by an average of 11% after four weeks.[ref]

• An RCT involving women with rheumatoid arthritis found that 500 mg/day reduced pain, stiffness, and TNF-alpha levels.[ref]

• A meta-analysis that combined the data from 7 clinical trials found a significant reduction in blood pressure in randomized controlled trials that used doses of more than 500mg/day.[ref]

Which of these anti-inflammatory supplements should you choose? The answer here is going to be an individual one. Realistically, for most people over age 50, the answer will depend on which one doesn’t interfere with whatever prescription medication you’re on. The other part of the picture is genetics, and if you have your genetic raw data, learning which inflammatory cytokines are likely to be upregulated gives you a good starting point.

My thought here - and again I could be wrong - is that switching between anti-inflammatory supplements may be the safe way to go. That way if the supplement has an unknown negative, I’m not taking high doses for years. So I take curcumin for a few weeks and then switch to hesperidin for a bit, etc.

Melatonin:

While most people think of melatonin as a sleep supplement, it does so much more than that in the body. The pineal gland produces lots of melatonin at night that then circulates through your brain, through your spinal fluid, and throughout your body via your bloodstream.

Melatonin plays multiple roles in the body: it sets your circadian rhythm at night, it acts as a strong antioxidant in your cells to prevent oxidative stress, and it modulates your immune response.

As we age, the pineal gland calcifies and we produce less melatonin at night. The other big modern factor that reduces melatonin production is our exposure to light in the blue wavelengths at night. LED lights, fluorescent lights, and our glowing TVs, cell phones, and tablets are all suppressing melatonin production and telling our bodies that it is still daylight.

Animal studies show benefits for Alzheimer’s prevention by clearing out amyloid-beta plaque and improving insulin signaling in the brain.[ref][ref][ref][ref][ref]

Clinical trials on melatonin (3-5mg/night) show the following:

• Reduced inflammatory cytokine levels (TNF-alpha) in women with PCOS.[ref]

• In an RCT involving MS patients, melatonin improved heart rate variability and improved oxidative stress biomarkers.[ref]

This is a great, in-depth overview of how melatonin interacts with the causes of aging.

Screenshot from https://pmc.ncbi.nlm.nih.gov/articles/PMC9204094/ - excellent to read

You can increase your endogenous melatonin production by avoiding light at night and by getting bright daylight first thing in the morning. Tryptophan is the precursor amino acid needed for melatonin production, so getting enough tryptophan in your diet is also important.

Alternatively - or in addition - melatonin supplements are readily available in the US. The clinical trials in people who have a chronic condition use larger doses, but for someone who is healthy and middle-aged, high doses likely aren’t needed. A very low dose option is Life Extention 300 mcg timed release, and Life Extention also offers a 1.5 mg immediate release/extended release option. The timed-release or extended-release options better mimic the natural production of melatonin throughout the night.

In my opinion, at a minimum, everyone should reduce their exposure to light in the evenings so that they will produce more melatonin at night and have a better circadian rhythm. You can decide if a supplemental melatonin product would give you further benefits.

Conclusion:

I think there are potentially high-impact, age-reversing therapeutics on the horizon, but for now, I’m sticking with the low-hanging fruit: decreasing inflammation, keeping my brain healthy, modulating immune function, and resolving inflammation when it happens.

What am I not doing? I’m not buying some of the snake oil out there… and I’m also not worried about biological age tests or biomarkers that I’m not sure of their impact.

*Affiliate links to Amazon products are offered examples to give you a starting point. Please do your own research, read reviews, and pick a supplement that works best for you.