Anima Books
books by holistic veterinarian Dr Christine King
Miscellany
Antioxidants
Can too much of a good thing be a bad thing?
Sometimes I need to head in the wrong direction for awhile in order to discover the right direction.
That's something I've learned about myself over the years. It's of a piece with some advice a farrier gave me many years ago, when he jokingly said:
“When what you're doing isn't working, do the opposite.”
And that brings me to antioxidants.
Twice in the past 20 years, I've had cause to wonder whether taking too many antioxidants, particularly too high a dose, can be a bad thing.
Specifically, I wondered why I felt worse (stiffer, more uncomfortable, more lethargic, etc.) after overdoing antioxidant supplements — which I had been taking because I wasn't feeling good!
The second incident occurred a few days ago. Thinking that my stiffness, widespread aches and pains, lethargy, malaise, disturbed sleep, slow recovery after exercise, and mental fog were simply a function of age [I had just turned 63], I had steadily increased the variety and dosage of antioxidants I was taking each day.
At the time, I was taking the following supplements:
* vitamin C — 2 grams/day, with orange juice
* vitamin D3 — 3,000 IU/day (cholecalciferol, 75 µg/day)
* vitamin E — 500 IU/day (d-alpha-tocopherol 335 mg/day)
* vitamin B complex — 1 sustained-release tablet/day, containing thiamine (B1, 100 mg), riboflavin (B2, 80 mg), nicotinamide (B3, 100 mg), pantothenic acid (B5, 110 mg), pyridoxine (B6, 62 mg), folate (400 µg), cyanocobalamin (B12, 100 µg), choline (50 mg), inositol (50 mg), biotin (50 µg), and vitamin C (200 mg)
* vitamin B12 — 3 mg (3,000 µg)/day, sublingual tablets or spray
* lysine — 1 tablet/day, containing lysine (800 mg), astragalus root extract (200 mg), vitamin C (250 mg), and zinc (12 mg)
krill oil — 1500 mg/day, supplying 180 mg EPA, 82.5 mg DHA, and 150 µg astaxanthin
The krill oil was a recent addition. I'd been on it for only a week, and thus far it had made no difference. (But I hadn't expected it to; it was a long-range strategy to help prevent cataracts.)
[I have a separate article on preventing age-related cataracts.]
So, with all these wonderful supplements, why was I sleeping poorly and waking up each morning feeling like I'm 80, and then dragging my tired ol' bones around all day, longing for my bed?
As that Garth Brooks song goes:
“I'm much too young to feel this damn old!”
. . .
Oh, and then there was the disturbing tingling and numbness in my feet in the mornings.
I'm a long-time vegetarian, so my mind immediately went to vitamin B12 deficiency. I'm vegetarian, not vegan, but while I do include some dairy products and eggs in my diet, I wasn't eating all that much of either.
And so I took way more B12 than is recommended. At first, I was taking an additional 1 mg (1,000 µg) per day, when the recommended daily intake for an adult is 2.4 µg. (Yes, you read that right: I was taking > 400 times as much as I should have needed.) But it didn't help.
My mum, who was a nurse and later a dietician, needed periodic B12 injections when she got older, as she said she lacked the intrinsic factor produced in the stomach that is necessary for absorption of B12 in the small intestine. Maybe I lack it, too, I thought; so maybe I can overcome this deficiency by taking a superabundance of B12.
I know; I know. Even smart people do dumb things sometimes!
However, the neurologic symptoms continued. I'd worked my way up to 5 mg (5,000 µg) per day before saying to myself, “This is ridiculous!”
Fortunately, B12 is water-soluble, and any excess is excreted in the urine, so the only downsides were the expense and the fact that I'd been chasing the wrong rabbit for way too long.
. . .
As my plethora of inexplicable problems persisted and gradually worsened — inexplicable because I had no illness or injury that would have explained any of it — I thought I'd add more antioxidants.
In short, the worse I felt, the more I took, thinking that all of my symptoms were caused or exacerbated by oxidative damage and the inflammation that ensues.
So, a few days ago I bought a high-potency turmeric supplement that is labelled for joint pain. It contains the following:
* turmeric — 814 mg curcuminoids
* boswellia — 52 mg
* ginger — 12 mg
* black pepper — 6 mg
That's per capsule. I took the label dose, which is 1 capsule/day.
Turmeric root: fresh (whole and sliced) and dried (powdered).
As I'd been for a jog in the park that morning and my multi-joint and -muscle pain was interfering with my ability to sit comfortably at the computer, I took a second capsule 2 hours after the first, thinking that I must be really low in antioxidants, especially after my run.
That evening, I took a third dose, thinking that I didn't want the earlier doses to wear off overnight and create a rebound effect of even more oxidative harm…
Yes, I know; I know! It is simply not true that if some is good, then more is better.
. . .
But making that mistake was actually a good thing, because I woke up the next morning feeling worse than ever!
An incident from 20 years ago, in which I did a similar thing — I took way more than the label dose of an antioxidant combo, and it made me feel far worse — came to mind.
And so I went looking online for information on whether a surfeit of antioxidants can cause the sorts of body-wide muscle and joint pain and the nebula of other symptoms I was experiencing.
The interesting thing is that I had to search and search and search! All I kept finding at first were web articles about how great antioxidants are; how essential for our health, for healthy aging, recovery after exercise, and all the rest.
But I kept looking, and finally I found a review paper by a group of exercise physiologists that answered my question:
Can too much of a good thing — in this case, antioxidants — be a bad thing?
Of course, the answer is yes!
And I learned a new term: Reductive stress.
It's similar to oxidative stress, in that it involves a surplus of reduced molecules, whereas oxidative stress involves a surplus of oxidized molecules.
'LEO goes GER' is the mnemonic device I use to remember which is which: lose electrons, oxidation (LEO); gain electrons, reduction (GER).
And surprisingly — that is, until I'd thought about it a bit — reductive stress can be just as harmful as oxidative stress.
Reductive stress occurs when excessive intake or production of antioxidant compounds interferes with the normal cycling of oxidation–reduction (red-ox or redox) reactions in a cell.
As normal red-ox cycling is essential for a whole slew of cellular processes, it's no wonder that I was feeling so crummy!
. . .
Antioxidants and exercise
Li S, Fasipe B, Laher I. Potential harms of supplementation with high doses of antioxidants in athletes. Journal of Exercise Science & Fitness, 2022; 20: 269–275.
The review paper, published in the October 2022 issue of the Journal of Exercise Science and Fitness, is about antioxidant supplementation in athletes.
I'm not a serious athlete, but I do like to keep fit. Not only am I vain enough to want to lose those few extra pounds and finally get back into my 'nice' jeans, I have a family history of osteoporosis, heart disease, type II diabetes, and cancer, to name just the hits. I'd like to avoid all of that!!
Here is the abstract (emphasis mine):
❝ Vigorous exercise generates large amounts of reactive oxygen species (ROS) as a result of the consumption of large volumes of O2 [oxygen] in athletes, causing some athletes to consume antioxidants in the erroneous belief that this will counteract the damaging effects of ROS.
There is currently no convincing evidence to support the benefits of antioxidant supplementation in acute physical exercise and exercise training. [i.e., in single or repeated bouts of exercise]
On the contrary, exogenous antioxidants prevent some physiological functions of free radicals that are needed for cell signaling, causing higher dosages of antioxidants to hamper or prevent performance-enhancing and health-promoting training adaptation such as mitochondrial biogenesis, skeletal and cardiac muscle hypertrophy, and improved insulin sensitivity.
However, there remains the perception that antioxidants can counterbalance oxidative stress and benefit exercise adaptation and performance in athletes. It is likely that the negative effects of high doses of antioxidant supplementation exceed their potential benefits. ❞
The thing is, the dosages they're calling “high” are much lower than I was taking — and I'm fairly conservative in my dosages compared with some of my colleagues and with various other sources of natural health information!
(More on those dosages later.)
The negative effects the authors discuss include these:
1. Poor adaptation to exercise
✔︎ No matter how much or what type of exercise I engaged in (cardio, strength training, agility, etc.), I failed to gain and even continued to lose muscle mass, strength, flexibility, and stamina — oh, and motivation!
I have a Master's degree in exercise physiology, so I know how to safely increase and maintain exercise capacity. And yet…!
2. Delayed post-exercise recovery
✔︎ I'd begun to have more muscle and joint stiffness and pain after exercise, even the types and amounts of exercise I had previously tolerated well and to which I should have been well-adapted.
In addition, it was taking an extra day or two for me to recover after a jog (which I'd taken up to preserve bone density) or a bout of strength training.
I had attributed all of this decline to age, and I'd simply resigned myself to becoming less and less capable. ☹︎
3. Defective autophagy
Autophagy — literally, self-eating or self-devouring — is a natural process by which damaged cell components are removed and replaced by healthy, new ones.
Pretty much all cell components undergo this process of renewal, from small molecules and proteins to entire organelles such as mitochondria (see below), and even cell membranes.
Over time, defective autophagy results in an accumulation of damaged or otherwise dysfunctional cells.
Not surprisingly, defective autophagy is involved in the aging process. It is also present in any number of degenerative conditions, including osteoarthritis; and in proliferative disorders, including tumor formation, persistence, recurrence, expansion, and metastasis (distant spread).
✔︎ I felt like I was aging at an accelerated rate, and I had aches and pains all over that were inexplicable (e.g., not associated with injury).
My skin had become more fragile and slow to heal after even minor wounds; and the areas of sun damage I've been so careful to protect for decades had begun to worry me.
I'd already had one squamous cell carcinoma in situ removed from my face; now it seemed to be recurring, and other areas I'd been watching were starting to look more abnormal, too.
4. Reduced mitochondrial biogenesis
This one deserves a good look. Even though it sounds complicated, it's the key to how well we feel and function, and to how well we age.
Mitochondria are the little power stations inside our cells. They have other functions, but energy production is their main purpose, and lack of energy is perhaps the most common and recognizable symptom of mitochondrial insufficiency.
Transmission electron microscopic (TEM) image and diagram of a mitochondrion (plural, mitochondria). Scale: nanometers (nm).
Mitochondrial biogenesis
Mitochondrial biogenesis is a natural process in which a cell increases the number of mitochondria it contains, in response to increased energy demand.
In short, the living cell (bio-) creates (genesis) more mitochondria when needed.
This increase in mitochondrial number is often referred to as an increase in mitochondrial density.
That's simply because the cell doesn't necessarily get any larger; it just contains more of these little organelles, which increases their 'density' as more are packed into the cell.
Endurance athletes, for example, have particularly high mitochondrial density in their working muscles, without being bulked up like body builders.
Reduced biogenesis is the opposite; and when combined with defective autophagy, it results in a decrease in mitochondrial number, size, and capacity. And that's not a good thing!
. . .
By the way, ginger root contains some bioactive molecules that promote mitochondrial biogenesis:
Deng X, Zhang S, Wu J, et al. Promotion of mitochondrial biogenesis via activation of AMPK-PGC1ɑ signaling pathway by ginger (Zingiber officinale Roscoe) extract, and its major active component 6-gingerol. Journal of Food Science, 2019; 84(8): 2101-2111.
❝ Ginger … is expected to be a long-term used dietary supplement and be developed into a new remedy for mitochondrial dysfunctional disorders. ❞
Happily, I love ginger! As I give this article one final read, I'm sipping on a cup of ginger tea, made from some fresh ginger root I found in my fridge. Yum!!
Ginger root: fresh (whole and sliced) and made into ginger tea.
Back to antioxidants
Anyway, back to antioxidants. Where they fit into all this is fairly straightforward.
I'll use aerobic exercise — physical activity that increases our oxygen demand, and thus our heart rate and respiratory rate and depth — as a template. Not only is that what the article focused on, it also relates to some of my most problematic and revealing symptoms.
During aerobic exercise, the demand for energy production in our working muscles is increased well above the resting rate. The greater the duration or intensity of exercise, the greater the demand for energy.
The production of energy for muscle contraction involves a biochemical chain-reaction in our mitochondria, called the mitochondrial respiratory chain, that generates reactive oxygen species (ROS). These very unstable and highly reactive little molecules are also known as free radicals and, more broadly, RONS (reactive oxygen and nitrogen species).
But while that may sound like a bad thing, the generation of ROS during exercise is actually a good thing in most circumstances, as it is adaptive. It stimulates mitochondrial biogenesis, which increases our exercise capacity.
Aerobic exercise stimulates mitochondrial biogenesis,
which increases our exercise capacity.
The generation of ROS also stimulates the production of antioxidants in our bodies, which keeps the red-ox cycle in balance.
It's basically the Goldilocks principle: an appropriate exercise regimen, and thus a red-ox dynamic, that's “juuust right.”
On the other hand, a sedentary lifestyle increases oxidative stress because it leads to a reduction in mitochondrial biogenesis and thus lower mitochondrial density and capacity. Lethargy and fatigue are the common experiences of low mitochondrial density and/or capacity.
The body is very economical with its resources, increasing or decreasing capacity according to demand. The phrase “use it or lose it” applies just as much to our anatomy and physiology (structure and function) as it does to anything else in our experience.
In short: no exercise, no stimulus for greater mitochondrial capacity.
So, here is one simple solution to the problem of oxidative stress: move more!
A sedentary lifestyle reduces mitochondrial biogensis,
which leads to lethargy and fatigue.
. . .
As for antioxidants and aerobic exercise, the authors summarized some key studies, showing that even moderate supplemental intake of certain antioxidants can be counterproductive. For example:
As soon as I read that article, I resolved to stop taking any more antioxidant supplements except the krill oil (which I kept taking until the very expensive bottle ran out), and instead eat more colorful fruits and veggies.
I already eat a wide variety of colorful fruits and veggies, and I am a dark-chocolate fiend, so I probably have a healthy antioxidant intake just from my fridge and freezer.
I also love wine, particularly red wine, but I'd cut out wine a few months prior, having listened to “the experts” who say that it's bad for my health. Cutting it out hadn't made any difference, though; and as I really enjoy wine, I picked up a bottle of red the day I read the exercise paper.
As I say about dog treats (and chocolate):
“It's good for the soul, if not for the body, and that's important, too!”
In fact, it may well be the whole ball game. But that's a story for another day.
. . .
The day I read that paper and resolved to stop taking any more antioxidant supplements, I also took myself out for some unscheduled aerobic exercise, for the sole purpose of generating a little more ROS to balance out the reductive stress I've evidently created with my imprudent antioxidant intake.
Within 24 hours of stopping the antioxidant supplements, I was already feeling so much better that it was a little alarming... I realized that I've been harming myself with my supplement intake!
Today, I feel better than I have in years!
How much of this improvement is psychosomatic and how much is biochemical?
Are these two concepts even as distinct and different as we customarily think?
I think not — but that, too, is a story for another day.
And I don't much care at this point. I feel good, and that changes everything!
Update: Day 6
It's been 6 full days since I stopped taking the supplements. The last dose was on a Tuesday evening; it is now Tuesday morning of the following week.
On Sunday morning, I woke up feeling so good that I was actually restless with energy. It's the same this morning. I realized that I'd gradually been restructuring my life for the low energy that had become normal for me over the past several years.
I'd gradually restructured my life for the low energy
that had become normal.
Sunday was a beautiful late-winter day, so I did some odd jobs in the garden that I'd been putting off for several months because they'd seemed like too much trouble, even too arduous, such as moving the compost pile and weeding a very overgrown area.
And so I overdid it — of course I did! I was feeling better than I had in decades, and I'm always impatient for improvement, so of course I overdid it. ☺︎
But the interesting thing is that I woke up the next morning with none of the usual after-effects of overexertion. In fact, I woke up feeling great!
I had the energy and the inspiration to go for a run in the park and then do some strength training — something I would never have been able to do a day after overdoing it with yard work. I also finished the last bit of weeding.
This morning I woke up feeling great again.
Knowing myself as I do, I can say with confidence that if this improvement is merely psychosomatic, then it would have worn off by now. I tend to get wildly enthusiastic about new things, but the excitement never lasts. Sooner or later — usually sooner rather than later — my old habits of thought take over and I'm back to square one.
If this improvement is merely psychosomatic,
then it would have worn off by now.
And yet, every day I wake up feeling brighter, stronger, more comfortable, and more free than I have in … I can't remember when! Since my 20s?!
Mentally, I've felt like I'm in my 20s (30 at most) ever since I was in my 20s. Mentally, I just don't feel my chronological age. And now my body is finally starting to read the memo!
One problem that has been particularly bothering me for the past 8 months or so has now all but disappeared. Chronic pain in my neck when I lie down has been disturbing my sleep for many months, and it has been steadily getting worse. I just can't get comfortable, and it's become impossible for me to lie on my right side without a really uncomfortable tingling and numbness developing in my right hand. It is severe enough that it even wakes me up in the middle of the night.
I had resigned myself to the fact that I must have some degenerative intervertebral disc disease in my lower cervical spine that is now impinging on the spinal nerves that supply my hand. The tingling and numbness in my feet when I first get out of bed in the morning has also been worse on the right than on the left, so I was fairly sure that I had some disc degeneration on the right.
But this morning I woke up and realized that I hadn't had any of the usual problems in my right hand overnight, and there was barely any tingling in my feet. I'd slept well and woken early, feeling refreshed and ready for the day. I can't remember when I last woke up feeling this way!
I can't remember when I last woke up feeling this way!
The other thing I've noticed is that I feel taller. Seriously. For several months now, I've been aware that I've shrunk, as “old people” tend to do, my spinal column compressing and contorting from the chronic tension throughout my spinal muscles, head to 'tail'.
But for the past several days, that has been reversing, as has the chronic tension in my hips, shoulders, legs, and arms. In short, I am longer now than I have been for the past several years. And more flexible, agile, and able.
Oh, and my memory and mental clarity have improved dramatically as well. I had been noticing with sadness that my ability to remember what I read just a few hours ago has been profoundly impaired. Each morning, I read the day's abstracts on PubMed that are of interest (my search term is 'horse or equine'). A few hours later, I'd struggle to remember what I'd read!
These improvements in my physical, mental, and yes even emotional well-being are quite frankly shocking to me. I had no idea that what I was taking in order to stave off the ravages of time were themselves ravaging my body and mind.
I had no idea that what I was taking in order to stave off
the ravages of time were themselves ravaging my body and mind.
It's been a most enlightening week…
