Meta Information
ID:calcium-akg-liposomal
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/chelating-antibiotics
Target name:
Chelating Antibiotics (Tetracyclines, Quinolones)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
The calcium ion binds to tetracycline and quinolone antibiotics in the gut, forming an insoluble complex that prevents the antibiotic from being absorbed and rendering it ineffective.
Actionable advice:
Calcium-AKG should be taken at least 2 hours before or 4 hours after these antibiotics.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Most antacids, except sodium bicarbonate, may decrease drug absorption by adsorption or chelation of other drugs.
Label source:
PubMed: Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. (PMID 10400401)
Action type:
separate
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Calcium salts significantly decrease the absorption of levothyroxine from the gastrointestinal tract, which can lead to inadequate thyroid hormone levels and treatment failure.
Actionable advice:
Doses of Calcium-AKG and levothyroxine should be separated by at least 4 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine.
Label source:
FDA label: Levothyroxine (Synthroid)
Action type:
separate
Target id:
/intervention/bisphosphonates
Target name:
Bisphosphonates (e.g., Alendronate)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
2
Description:
Calcium binds to bisphosphonate drugs in the gut, dramatically reducing their absorption and effectiveness in treating bone density loss. Bisphosphonates must be taken on an empty stomach.
Actionable advice:
Calcium-AKG should be taken at least 2 hours after the bisphosphonate dose.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day
Label source:
FDA label: Risedronate (Actonel)
Action type:
separate
Target id:
/condition/renal-impairment
Target name:
Renal Impairment / Kidney Disease
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Impaired kidneys cannot effectively regulate blood calcium levels, making supplementation risky and increasing the likelihood of dangerous hypercalcemia and soft tissue calcification.
Actionable advice:
Calcium-AKG should be avoided unless specifically directed and monitored by a nephrologist.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Importantly, increasing evidence suggests that calcium supplementation may enhance soft tissue calcification and cardiovascular disease in CKD-MBD. Further research is needed to elucidate the risks and mechanisms of soft tissue calcification with calcium supplementation in both healthy subjects and CKD-MBD patients.
Label source:
PubMed: Clinical journal of the American Society of Nephrology : CJASN (2010)
Source url:
Exact phrase from label:
The existing data are concerning for the role of calcium supplementation and calcium binder use in patients with renal compromise.
Label source:
PubMed: Expert opinion on drug safety (2014)
Source url:
Exact phrase from label:
Calcium supplementation also appears to accelerate vascular disease in patients with renal impairment, including those not yet requiring dialysis.
Label source:
PubMed: Climacteric : the journal of the International Menopause Society (2008)
Action type:
avoid
Target id:
/condition/hypercalcemia
Target name:
Hypercalcemia (High Blood Calcium)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Supplementing with calcium when blood calcium levels are already high will worsen the condition, increasing risks of kidney stones, cardiac issues, and cognitive changes.
Actionable advice:
Calcium-AKG should not be taken with a history of or current hypercalcemia.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
To avoid iatrogenic suppression of PTH levels, high calcium load and potential affection of the kidney function, a reduction scheme should be actively recommended by thyroid surgeons.
Label source:
PubMed: Calcium and vitamin D substitution for hypoparathyroidism after thyroidectomy - how is it continued after discharge from hospital? (PMID 39636417)
Action type:
avoid
Target id:
/intervention/digoxin
Target name:
Digoxin
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High blood calcium levels (hypercalcemia), which can be caused by calcium supplementation, increase the effects of digoxin on the heart, raising the risk of serious digoxin toxicity.
Actionable advice:
High-dose calcium supplements should be avoided, and it is important to talk to a cardiologist before using Calcium-AKG.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Bradycardia and heart block caused by digoxin are
parasympathetically mediated and respond to atropine.
Label source:
Action type:
avoid
Target id:
/class/diuretics
Target name:
Thiazide Diuretics (e.g., Hydrochlorothiazide)
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Thiazide diuretics decrease the amount of calcium excreted in the urine. When combined with calcium supplements, this can lead to excessively high levels of calcium in the blood (hypercalcemia).
Actionable advice:
It is important to consult a doctor before combining; regular monitoring of blood calcium levels is required.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Exact phrase from label:
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism.
Label source:
FDA label: Hydrochlorothiazide (Microzide)
Action type:
monitor
Target id:
/intervention/iron-bisglycinate
Target name:
Iron Supplements
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Calcium and non-heme iron compete for the same absorption pathways in the small intestine, leading to significantly reduced absorption of iron when taken together.
Actionable advice:
Doses of Calcium-AKG and iron supplements should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Although previous studies have shown that Ca inhibits acute Fe absorption, there is no evidence of the possible long- or medium-term effects of Ca supplementation on Fe bioavailability.
Label source:
PubMed: One-month of calcium supplementation does not affect iron bioavailability: a randomized controlled trial. (PMID 24290597)
Action type:
separate
Target id:
/intervention/vitamin-d
Target name:
Vitamin D
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin D is essential for the absorption of calcium from the gut into the bloodstream. Without adequate Vitamin D, calcium supplementation is less effective and potentially riskier.
Actionable advice:
It is a good idea to maintain adequate Vitamin D levels through sun, diet, or supplements when taking Calcium-AKG.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: Vitamin D plus calcium is superior to no therapy or calcium alone in the management of corticosteroid-induced osteoporosis.
Label source:
PubMed: The role of vitamin D in corticosteroid-induced osteoporosis: a meta-analytic approach. (PMID 10446876)
Action type:
informational_none
Target id:
/intervention/vitamin-k2
Target name:
Vitamin K2
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin K2 activates proteins that help direct absorbed calcium into bones and teeth and away from arteries and soft tissues, which is critical for cardiovascular and skeletal health.
Actionable advice:
Co-supplementation with Vitamin K2 is strongly recommended to ensure proper calcium utilization.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
vitamin K2 can optimize calcium use in the body, preventing any potential negative health impacts associated with increased calcium intake. Osteoblasts produce osteocalcin, which helps take calcium from the blood circulation and bind it to the bone matrix. The newly made osteocalcin, however, is inactive, and it needs vitamin K2 to become fully activated and bind calcium.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC4566462/
Action type:
informational_none
Target id:
/biomarker/serum-calcium
Target name:
Serum Calcium Levels
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Long-term supplementation with any calcium salt can potentially elevate serum calcium levels above the normal range, a condition known as hypercalcemia, which requires medical attention.
Actionable advice:
Periodically monitor serum calcium levels with your doctor when taking Calcium-AKG long-term.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
High dietary Ca-P supplementation linearly improved indicators of mineral retention and bone regulation.
Label source:
PubMed: Dietary calcium and phosphorus levels in lactating Shenxian sows regulate growth performance and bone metabolism in suckling piglets. (PMID 42182911)
Action type:
monitor
Target id:
/class/dmt1-competing-minerals
Target name:
Other Divalent Minerals (Zinc, Magnesium)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High doses of calcium can compete with other minerals like zinc and magnesium for absorption in the gut, potentially reducing their bioavailability if taken at the same time.
Actionable advice:
For optimal absorption, Calcium-AKG and zinc or magnesium supplements are best separated by 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In humans, increasing dietary calcium has been shown to depress magnesium absorption, particularly in very-low-birth-weight infants, where high calcium intakes can lead to magnesium deficiency compared to in utero accretion rates.
Label source:
Primary literature: https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mineral-absorption
Action type:
separate
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
2
Description:
Meals high in phytates (grains, legumes) or oxalates (spinach) can bind to calcium, reducing its absorption. Taking it on an empty stomach may ensure maximal absorption of the AKG component.
Actionable advice:
It is best taken on an empty stomach, at least 1 hour before or 2 hours after a meal.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Vegetarians who consume greater amounts of vegetables will have a higher intake of oxalates, which may reduce calcium availability.
Label source:
PubMed: Oxalate content of foods and its effect on humans. (PMID 24393738)
Action type:
separate
Target id:
/dietary/fasting-state
Target name:
Fasted State
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Alpha-ketoglutarate may activate cellular pathways similar to those engaged during fasting (e.g., AMPK). Taking it in a fasted state could theoretically enhance its longevity-related benefits.
Actionable advice:
A daily dose is generally best taken in the morning while in a fasted state for potential synergistic effects.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging.
Label source:
Action type:
informational_none
Target id:
/class/calcium-channel-blockers
Target name:
Calcium Channel Blockers
Severity:
minor
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Theoretically, very high levels of supplemental calcium could compete with calcium channel blocker medications at their site of action, potentially reducing their effectiveness in lowering blood pressure.
Actionable advice:
It is a good idea to check blood pressure if taking high doses of Calcium-AKG with these medications.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the
transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.
Label source:
Action type:
monitor
Target id:
/dietary/hot-foods-beverages
Target name:
Hot Foods or Beverages
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Liposomal calcium-AKG relies on a heat-sensitive phospholipid bilayer to protect and deliver its payload. Stirring it into a hot beverage (coffee, tea, soup) can melt or rupture the liposomes, destroying the enhanced-absorption advantage that is the entire point of the liposomal form.
Actionable advice:
Liposomal calcium-AKG should not be added to hot drinks or food. It should be taken with cool or room-temperature liquid to keep the liposomes intact.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanism / liposome thermal stability
Exact phrase from label:
Phospholipid liposomal delivery systems are thermally labile and lose bilayer integrity when exposed to hot liquids, negating the absorption advantage of the liposomal format.
Label source:
Mechanistic inference
Action type:
avoid
Derived From
calcium-akg
Provenance Note
Interactions duplicated from 'calcium-akg'. Liposomal formulation; same interactions.